Elevated Glucose Research Articles

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

Elevated blood glucose levels are associated with the progression of brain hypometabolism, and HDL-C and APOE4 add to this association.

Brain glucose hypometabolism has consistently been found in neurodegenerative disorders, including Alzheimer's disease (AD). High blood glucose and HDL cholesterol (HDL-C) levels have also been linked to neurodegeneration and AD. However, there is limited understanding of the relationships between dementia-related risk factors in the brain and blood. A linear mixed model was used to examine the relationship between blood glucose and HDL-C levels and the progression of brain hypometabolism, adjusting for APOE4 and other clinical covariates. The hypometabolic convergence index (HCI) was measured by fluorodeoxyglucose-18 (FDG) positron emission tomography (PET) in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Data visualizations were generated to understand the joint effects of plasma glucose, HDL-C, and APOE4 on HCI. There were 336 individuals (781 observations), of whom 22.62% had AD. The majority were male (63.98%) and of white race, and 48.51% were carriers of APOE4. Over time, high blood glucose level was associated with the progression of brain glucose hypometabolism (β=0.33, 95% CI: 0.02, 0.64, p<0.05). A high plasma HDL-C level (β=1.22, 95% CI: 0.09, 2.35, p<0.05), more study visits (β=1.67, 95% CI: 1.37, 1.98, p<0.001), and being an APOE4 allele carrier (β=1.29, 95% CI: 0.15, 2.42, p<0.05) were also significant predictors of brain hypometabolism progression. APOE4 carrier status and number of visits account for the largest proportion of the variance from the fixed effects model. Random effects due to participant characteristics and fixed effects together accounted for 95.2% of the model variance. Subgroup analysis revealed that these effects were observed only in those without AD. High plasma glucose levels facilitated the progression of brain hypometabolism. The effect was more prominent in the APOE4 double-carriers with elevated HDL-C. Elevated blood glucose may reflect systemic insulin resistance, which could impair brain glucose uptake, resulting in brain hypometabolism. Controlling blood glucose and HDL-C levels in APOE4 carriers may improve brain metabolism, potentially delaying the onset of dementia.

Synthesis, molecular modelling, and biological evaluation of novel quinoxaline derivatives for treating type II diabetes

Quinoxalines are benzopyrazine derivatives with significant therapeutic impact in the pharmaceutical industry. They proved to be useful against inflammation, bacterial, fungal, viral infection, diabetes and other applications. Very recently, in January 2024, the FDA approved new quinoxaline containing drug, erdafitinib for treatment of certain carcinomas. Despite the diverse biological activities exhibited by quinoxaline derivatives and the role of secretory phospholipase A2 (sPLA2) in diabetes-related complications, the potential of sPLA2-targeting quinoxaline-based inhibitors to effectively address these complications remains unexplored. Therefore, we designed novel sPLA2- and α-glucosidase-targeting quinoxaline-based heterocyclic inhibitors to regulate elevated post-prandial blood glucose linked to patients with diabetes-related cardiovascular complications. Compounds 5a–d and 6a–d were synthesised by condensing quinoxaline hydrazides with various aryl sulphonyl chlorides. Biological screening revealed compound 6a as a potent sPLA2 inhibitor (IC50 = 0.0475 µM), whereas compound 6c most effectively inhibited α-glucosidase (IC50 = 0.0953 µM), outperforming the positive control acarbose. Moreover, compound 6a was the best inhibitor for both enzymes. Molecular docking revealed pharmacophoric features, highlighting the importance of a sulfonohydrazide moiety in the structural design of these compounds, leading to the development of potent sPLA2 and α-glucosidase inhibitors. Collectively, our findings helped identify promising candidates for developing novel therapeutic agents for treating diabetes mellitus.

Computational Modeling of Sodium-Ion-Channel-Based Glucose Sensing Biophysics to Study Cardiac Pacemaker Action Potential

Elevated blood glucose levels, known as hyperglycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding the internal mechanisms has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing biophysics mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment computational model of the human pacemaker action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on pacemaker action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the pacemaker action potential frequency. In summary, our mathematical model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.

Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy

BackgroundThe aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30.MethodsThe study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure.ResultsOut of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery.ConclusionAlthough there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

A Systematic Review of Gut Microbiota Diversity: A Key Player in the Management and Prevention of Diabetes Mellitus.

Diabetes mellitus represents a significant global health challenge, characterized by impaired insulin production and action, leading to elevated blood glucose levels. This systematic review investigates the association between gut microbiota composition and diversity, along with the structural and functional characteristics of the gut microbiome, and their implications for the risk, prevention, and management of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive search across multiple databases yielded 16 studies that met the inclusion criteria. The findings highlight the potential of gut microbiota interventions, such as fecal microbiota transplantation and probiotic supplementation, in improving metabolic parameters and glycemic control. Notably, the review underscores the importance of dietary interventions and the role of specific microbial populations in influencing diabetes outcomes. Despite the promising results, the variability in study designs, sample sizes, and methodologies poses challenges for generalizability and interpretation. This review emphasizes the need for further research to elucidate the mechanisms underlying these associations and to explore personalized microbiome-based therapies in diabetes management. The insights gained could pave the way for innovative therapeutic strategies aimed at harnessing gut health to mitigate the burden of diabetes mellitus.

Effects of GABA on Oxidative Stress and Metabolism in High-Glucose Cultured Mongolian Sheep Kidney Cells.

The Mongolian sheep, emblematic of the Inner Mongolian grasslands, is renowned for its exceptional stress resistance and adaptability to harsh environments, drawing considerable attention. Recent research has unveiled the novel role of γ-aminobutyric acid (GABA) in combating oxidative stress. This investigation examined how GABA impacts renal-cortex and medulla cells from Mongolian sheep exposed to high-glucose stress conditions, utilizing gene expression analysis and non-targeted metabolomics. Elevated glucose levels significantly reduced the viability of Mongolian sheep renal cells and increased reactive oxygen species (ROS) levels. Conversely, the introduction of GABA notably enhanced cell viability, reduced ROS production, and stimulated the expression of antioxidant genes (e.g., Gpx, SOD, CAT) in the renal cortex. In the renal medulla, CAT expression increased, while Gpx gene expression showed mixed responses. Metabolomics analysis indicated that high-glucose exposure altered various metabolites, whereas GABA alleviated the metabolic stress induced by high glucose through modulating glycolysis and the tricarboxylic acid cycle. In Mongolian sheep renal cells, GABA effectively mitigated oxidative damage triggered by high-glucose stress by upregulating antioxidant genes and regulating metabolic pathways, revealing insights into its potential mechanism for adapting to extreme environments. This finding offers a fresh perspective on understanding the stress resilience of Mongolian sheep and may provide valuable insights for research across diverse disciplines.

Utility of photoplethysmography in detecting elevated blood glucose among non-diabetics.

This study aimed to evaluate a technique of using photoplethysmography (PPG) for detecting elevated blood glucose in individuals. This is a prospective, cross-sectional study in which 500 healthy volunteers were recruited at a tertiary hospital in Singapore from October 2021 to February 2023. Capillary glucose was measured concurrently with PPG signals acquired using the wrist-worn Actxa Tracker (Spark + Series 2) and the In-Ear Prototype model SVT, which were worn for a duration of 8 min. Participants with a capillary blood test reading ≤11.1 mmol/dL had to consume a standard glucose tolerance drink and return 1 h later for a second capillary blood test. Two hundred and forty-four features were subsequently extracted from the PPG signals. Of the 500 volunteers, 17 were excluded because of incomplete records. This led to a total of 483 participants' records being included in the final analysis. For predicting elevated capillary blood glucose level, demographics alone achieved an area under the curve (AUC) of 0.75. When wearable features derived from PPG were combined with demographics, AUC improved significantly to 0.82 (P = 0.0001). This study shows that a non-invasive method of assessing diabetes mellitus risk using PPG combined with demographics is a viable option to provide a cheaper and more accessible modality for population-wide diabetes mellitus risk assessment.

Relationship Between Pre-Diabetes and Gum Disease

Background: Pre-diabetes is a condition characterized by elevated blood glucose levels that are not yet high enough to be classified as diabetes. This intermediary stage increases the risk of progression to type 2 diabetes and is associated with various complications, including periodontal disease. Understanding the relationship between pre-diabetes and periodontal health is critical for developing effective prevention and management strategies.Objective: To explore the relationship between pre-diabetes and gum disease, evaluating the prevalence and types of periodontal complications in pre-diabetic patients.Methods: A retrospective analysis was conducted on clinical records of 150 patients diagnosed with pre-diabetes from 2018 to 2022. Data were collected on periodontal conditions, including gingivitis, periodontitis, bleeding gums, and tooth loss. Statistical analyses, including chi-square tests and logistic regression, were performed using SPSS version 25 to evaluate the association between periodontal complications and demographic factors.Results: Gingivitis was present in 12% of patients, periodontitis in 15%, bleeding gums in 8%, and tooth loss in 5%. Significant associations were found between periodontal complications, older age, and longer duration of pre-diabetes (p &lt; 0.05).Conclusion: Pre-diabetic patients exhibited a high prevalence of periodontal complications, highlighting the need for early periodontal assessment and management to prevent disease progression

Summary of the 2023 European Society of Cardiology clinical guidelines on the management of cardiovascular disease in patients with diabetes mellitus

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Navigating the Intersection of Glycemic Control and Fertility: A Network Perspective.

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and are implicated in various diseases. This article explores the relationship between glycemic control and AGE accumulation, focusing on fertility implications. A computational model using network theory was developed, featuring a molecular database and a network with 145 nodes and 262 links, categorized as a Barabasi-Albert scale-free network. Three main subsets of nodes emerged, centered on glycemic control, fertility, and immunity, with AGEs playing a critical role. The transient receptor potential vanilloid 1 (TRPV1), a receptor expressed in several tissues including sperm, was identified as a key hub, suggesting that the modulation of TRPV1 in sperm by AGEs may influence fertility. Additionally, a novel link between glycemic control and immunity was found, indicating that immune cells may play a role in endocytosing specific AGEs. This discovery underscores the complex interplay between glycemic control and immune function, with significant implications for metabolic, immune health, and fertility.

Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy: Network pharmacology analysis and experimental validation.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Its blindness rate is high; therefore, finding a reasonable and safe treatment plan to prevent and control DR is crucial. Currently, there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects. To investigate the effects of Buqing granule (BQKL) on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments. This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions (PPI), identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and preliminarily validated the screened core targets by molecular docking. Furthermore, we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection, and administered the appropriate drugs for 12 weeks after the model was successfully induced. Body mass and fasting blood glucose and lipid levels were measured, and pathological changes in retinal tissue were detected by hematoxylin and eosin staining. ELISA was used to detect the oxidative stress index expression in serum and retinal tissue, and immunohistochemistry, real-time quantitative reverse transcription PCR, and western blotting were used to verify the changes in the expression of core targets. Six potential therapeutic targets of BQKL for DR treatment, including Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3, were screened using PPI. Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment. Molecular docking prediction indicated that BQKL stably bound to these core targets. In vivo experiments have shown that compared with those in the Control group, rats in the Model group had statistically significant (P < 0.05) severe retinal histopathological damage; elevated blood glucose, lipid, and malondialdehyde (MDA) levels; increased Caspase-3, c-Jun, and TP53 protein expression; and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, ganglion cell number, AKT1, MAPK1, and MAPK3 protein expression. Compared with the Model group, BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids, MDA level, Caspase-3, c-Jun and TP53 proteins were reduced, while the expression of SOD, GSH-Px level, the number of ganglion cells, AKT1, MAPK1, and MAPK3 proteins were elevated. These differences were statistically significant (P < 0.05). BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

Bioassay guided isolation and compounds identification of the anti-diabetic fractions of (rosemary) Rosmarinus officinalis leaves extract

BackgroundDiabetes mellitus is a metabolic disease characterized by prolonged elevated blood glucose levels. It is a common health problem with a high mortality and morbidity to the human race. A number of medicinal plants such as rosemary (Rosmarinus officinalis) have been used for the treatment of diabetes. Most of the anti-diabetic conventional drugs have been found to have some side effects and there is therefore need to explore new sources of anti-diabetic drugs. The aim of the current study was to investigate the possibility of getting anti-diabetic compounds from R. officinalis that can be used as leads for drug discovery.MethodologyR. officinalis leaves were macerated in 50% methanol in dichloromethane and the crude extract fractionated by column chromatography. The obtained fractions were subjected to an in-vitro alpha-amylase inhibition assay. The anti-hyperglycemic potential of the fractions was evaluated in diabetic induced Wistar rats. The most potent fractions were analyzed by gas chromatography-mass spectrophotometry (GC-MS) for identification of the compounds.ResultsA total of 21 chromatographic fractions were assembled with different alpha- amylase inhibition activity. Eleven of the fractions had more than 30% alpha-amylase inhibition activity. The ethyl acetate fraction had the highest inhibition potential (LC50 of 2.8 μg/mL). The anti-diabetic assay in rats showed that fractions (F1) and (F4) had highest blood glucose reduction of 44.5 ± 0.4 and 52.8 ± 1.3%, respectively (p < 0.05). GC-MS analysis of fractions F1 and F4 showed the presence of 21 and 23 compounds in F1 and 23, respectively.ConclusionThis study has demonstrated that R. officinalis crude extract fractions obtained from 50% methanol in dichloromethane possesses alpha-amylase inhibitory and anti-hyperglycemic activities as well as secondary metabolites with varying chemical structures. The hexane and hexane/ethyl acetate (8/2) fractions showed most potent alpha-amylase inhibition with high anti-hyperglycemic activity giving hope of a possibility of obtaining lead compounds for new anti-diabetic drugs.

Protein kinase C iota promotes glycolysis via PI3K/AKT/mTOR signalling in high grade serous ovarian cancer.

Epithelial ovarian cancer, especially high grade serous ovarian cancer (HGSOC) is by far, the most lethal gynecological malignancy with poor prognosis and high relapse rate. Despite of availability of several therapeutic interventions including poly-ADP ribose polymerase (PARP) inhibitors, HGSOC remains unmanageable and identification of early detection biomarkers and therapeutic targets for this lethal malady is highly warranted. Aberrant expression of protein kinase C iota (PKCί) is implicated in many cellular and physiological functions involved in tumorigenesis including cell proliferation and cell cycle deregulation. Two high grade serous ovarian cancer cells SKOV3 and COV362 were employed in this study. PKCί was genetically knocked down or pharmacologically inhibited and several functional and biochemical assays were performed. We report that PKCί is overexpressed in HGSOC cells and patient tissue samples with a significant prognostic value. Pharmacological inhibition of PKCί by Na-aurothiomalate or its shRNA-mediated genetic knockdown suppressed HGSOC cell proliferation, EMT and induced apoptosis. Moreover, PKCί positively regulated GLUT1 and several other glycolytic genes including HK1, HK2, PGK1, ENO1 and LDHA to promote elevated glucose uptake and glycolysis in HGSOC cells. Mechanistically, PKCί drove glycolysis via PI3K/AKT/mTOR signalling. Na-aurothiomalate and highly selective, dual PI3K/mTOR inhibitor dactolisib could serve as novel anti-glycolytic drugs in HGSOC. Taken together, our results indicate PKCί/PI3K/AKT/mTOR signalling cascade could be a novel therapeutic target in a lethal pathology like HGSOC.

Hyaluronic acid methacryloyl/chitosan methacryloyl/3-methacrylamidophenylboronic acid multifunctional hydrogel loading exosome for diabetic wound healing

The management of diabetic wounds presents a formidable challenge in clinical settings due to elevated glucose levels, drug-resistant bacterial infections, and a deficiency of bioactive molecules in the microenvironment. To address this challenge, a glucose-responsive Hyaluronic acid Methacryloyl (HAMA)-Chitosan Methacryloyl (CSMA)-3-Methacrylamidophenylboronic acid (MPBA) loading Exosome (H-C-M@Exo) multifunctional hydrogel has been developed to enhance diabetic wound healing in this study. The H-C-M@Exo hydrogel exhibits remarkable features, including high hydrophilicity, excellent pressure resistance, antibacterial properties, and good biocompatibility. It uniquely possesses the ability to sustain the release of exosomes in response to glucose fluctuations. The H-C-M@Exo hydrogel can effectively reduce inflammation, significantly promote rapid re-epithelization, facilitate favorable collagen deposition, and stimulate abundant angiogenesis at the wound sites. Furthermore, the hydrogel induces localized regulation of M2 macrophage polarization, synergistically promoting diabetic angiogenesis and wound healing. These findings suggest H-C-M@Exo hydrogel is a promising biomaterial for the treatment of chronic diabetic wounds.

A field study to optimize protein and lipid levels in diet for cage-cultured subadult rockfish Sebastes schlegelii

A feeding trial was conducted to evaluate growth, body composition, serum biochemistry, digestion and metabolism, and oxidation resistence of S. schlegelii fed 9 diets in a 3×3 factorial design (protein levels: 44 %, 48 %, 52 %; lipid levels: 6 %, 10 %, 14 %), to optimize protein and lipid levels for practical feed formula. Rockfish (114.25 g) were stocked into 27 cages in an offshore system and fed test diets to satiation twice daily for 8 weeks. Growth increased but feed conversion rate decreased with dietary protein increasing. Increasing dietary protein to >48 % led to reduced feeding intake but increased protein efficiency ratio. Lipid efficiency ratio increased with dietary protein increasing but decreased with dietary lipid increasing. Hepatosomatic index decreased coupling with the increases in condition factor and liver lipid content as dietary lipid increased to 14 %. Intraperitoneal fat ratio increased with dietary lipid increasing. Increasing dietary protein to > 48 % significantly elevated serum total protein and glucose concentrations, hepatic glycogen synthase activity. High-protein (52 %) diets elevated serum albumin and urea nitrogen concentrations, hepatic pyruvate kinase and alanine aminotransferase (ALT) activities but downregulated hepatic growth-hormone (GH) receptor. Activities of trypsin, lipase, serum superoxide dismutase and total antioxidant capacity decreased with the dietary lipid increasing. Increasing dietary lipid to > 10 % reduced serum GH concentration, and high-lipid (14 %) diets significantly enhanced serum triglyceride concentration and hepatic transaminases activities, and resulted in a visual increase of adipocytes in liver. Serum cholesterol and low-density lipoprotein decreased as dietary protein increased to 48–52 % or dietary lipid >10 %. Hepatic succinate dehydrogenase activity and serum IGF-1 significantly increased while hepatic fatty acid synthetase decreased as dietary protein increased to >48 % or dietary lipid >10 %. High-protein (52 %) diet or high-lipid (14 %) diet elevated serum malonaldehyde concentration. These findings suggested 48 % protein and 10 % lipid were the optimal in diet for subadult S. schlegelii.

Sex-specific associations between total and regional Fat-to-muscle Mass ratio and cardiometabolic risk: findings from the China National Health Survey

BackgroundThe fat-to-muscle mass ratio (FMR), integrating the antagonistic effects of fat and muscle mass, has been suggested as a valuable indicator to assess cardiometabolic health independent of overall adiposity. However, the specific associations of total and regional FMR with cardiometabolic risk are poorly understood. We aimed to examine sex-specific associations of total and regional FMR with single and clustered cardiometabolic risk factors (CRFs).Methods13,505 participants aged 20 years and above were included in the cross-sectional study. Fat mass and muscle mass were assessed using a bioelectrical impedance analysis device. FMR was estimated as fat mass divided by muscle mass in corresponding body parts (whole body, arm, leg, and trunk). Clustered CRFs was defined as the presence of two or more risk factors, including hypertension, elevated blood glucose, dyslipidemia, insulin resistance (IR), and hyperuricemia. IR was assessed by the triglyceride glucose (TyG) index. Multivariable logistic regression models were applied to explore the associations of FMR in the whole body and body parts with single and clustered CRFs.ResultsThe odds ratios (ORs) increased significantly for all single and clustered CRFs with the per quartile increase of total and regional FMR in both sexes (P for trend < 0.001), following adjustment for confounders. Among the regional parts, FMRs of the legs presented the strongest associations for clustered CRFs in both men and women, with adjusted OR of 8.54 (95% confidence interval (CI): 7.12–10.24) and 4.92 (95% CI: 4.24–5.71), respectively. Significant interactions (P for interaction < 0.05) were identified between age and FMRs across different body parts, as well as between BMI status and FMRs in different regions for clustered CRFs. Restricted cubic splines revealed significant non-linear relationships between FMRs of different body parts and clustered CRFs in both sexes (P for nonlinear < 0.05).ConclusionsFMRs in the whole body and different regions were significantly associated with single and clustered CRFs in the general Chinese population. The association between FMR and clustered CRFs was more pronounced in youngers than in the elderly.

Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome

Globally, approximately 6–20 % of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10 mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

The key metabolic signatures and biomarkers of polycyclic aromatic hydrocarbon-induced blood glucose elevation in chinese individuals exposed to diesel engine exhaust

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention.